Synthesis, Biological Evaluation and Binding Studies of New Flavone Derivatives as Adenosine A2b Receptor Antagonists

Abstract

A series of eleven flavone derivatives were synthesized. The synthesized compounds were characterized structurally by various techniques using spectral analyses. All of the synthesized compounds were subjected to MTT proliferation assay to investigate their in-vitro cytotoxic activity. Among all the studied compounds, compounds, VIi, VIh, VId and VIk revealed moderate growth inhibitory effect towards the MDA-MB 231 cell line compared to the reference, doxorubicin. These compounds showed cytotoxicity activity with IC 50 values ranging from 43.7 to 138 µM in MDA-MB 231 cell line. The results of cytotoxic activity revealed that flavone derivatives with N-aryl acetamide substituted at the 3-position of flavone backbone have better cytotoxic activity. Moreover, the highest activity was observed with compound VIi that has oxy-N-pyriden-2-yl acetamide substituent at the 3-position of flavone backbone followed by compound VIh with IC 50 values of 43.7 and 50 μM, respectively. The biological activity results were elucidated by molecular docking studies using the homology model of the human adenosine A 2B receptor. As a result, the present study has highlighted that the bicyclic moiety of the compounds attached to hydrogen bond donor-acceptor capability and π-π stacking is an attractive scaffold for obtaining cytotoxic activity.

Selene-Ethylenelacticamides and N-Aryl-Propanamides as Broad-Spectrum Leishmanicidal Agents

“…The 77 molecules in this study were obtained through synthesis, with 48 new compounds, referred to as selene-ethylenelacticamides, derived from ethylenelactic acid (30–77). The remaining 29 compounds, N -arylpropanamides derivatives, are already reported by Sherbiny and Collaborators (2016) [ 20 ] and Huang (2021) [ 21 ] (1–29). Figure 3 displays the structure of each compound.…”

“…The test series was composed of a total of 77 compounds of synthetic origin, obtained through organic synthesis, with 48 new compounds derived from ethylenelactic acid and called selene-ethylenelacticamides. The remaining 29 compounds corresponded to N -arylpropanamides (which are the intermediates in the organic synthesis) and are compounds already reported in Sherbiny and Collaborators (2016) [ 20 ] and Huang and Collaborators (2021) [ 21 ]. All compounds were selected by their chemical and biological data, adhering to the workflows elaborated by Fourches et al [ 22 , 23 ].…”